Sjogren's disease is a common autoimmune disorder with significant morbidity and mortality secondary to destruction of the salivary and lachrymal glands. It involves both local and systemic autoimmunity and is generally recognized only after salivary and lachrymal glands are destroyed resulting in dry mouth and dry eyes (Borchers, A. T., S. M. Naguwa, C. L. Keen, and M. E. Gershwin. 2003 Immunopathogenesis of Sjogren's syndrome. Clin Rev Allergy Immunol 25:89-104; Delaleu, N., R. Jonsson, and M. M. Koller. 2005. Sjogren's syndrome. Eur J Oral Sci 113:101-113). Sjögren's syndrome is a common syndrome affecting 0.5% of the population with a strong female predominance (Delaleu, N., R. Jonsson, and M. M. Koller. 2005. Sjogren's syndrome. Eur J Oral Sci 113:101-113, Fox, R. I. 2005. Sjogren's syndrome. Lancet 366:321-331.). It consists of xerostomia and xerophthalmia and may be due to several causes including aging, infections, medications, environmental toxins and autoimmune responses (Daniels, T. E. 2000. Evaluation, differential diagnosis, and treatment of xerostomia. J Rheumatol Suppl 61:6-10). Sjögren's disease is a primary disorder consisting of Sjogren's syndrome with systemic manifestations including lymphadenopathy, interstitial pneumonitis and mild renal disease (Borchers, A. T., S. M. Naguwa, C. L. Keen, and M. E. Gershwin. 2003. Immunopathogenesis of Sjögren's syndrome. Clin Rev Allergy Immunol 25:89-104; Delaleu, N., R. Jonsson, and M. M. Koller. 2005. Sjögren's syndrome. Eur J Oral Sci 113:101-113). Sjögren's syndrome is often seen in association with other autoimmune diseases, especially systemic lupus erythematosus (SLE) (Manoussakis, M. N., et al. Moutsopoulos. 2004. Sjogren's syndrome associated with systemic lupus erythematosus: clinical and laboratory profiles and comparison with primary Sjogren's syndrome. Arthritis Rheum 50:882-891). Patients with Sjögren's disease often have hypergammaglobulinemia, and various autoantibodies, especially to Ro and La (Fox, R. I. 2005. Sjogren's syndrome. Lancet 366:321-331, Lazarus, M. N., and D. A. Isenberg. 2005. Development of additional autoimmune diseases in a population of patients with primary Sjogren's syndrome. Ann Rheum Dis 64:1062-1064, ansen, A., P. E. Lipsky, and T. Dorner. 2005. Immunopathogenesis of primary Sjogren's syndrome: implications for disease management and therapy. Curr Opin Rheumatol 17:558-565). Almost 4% of patients with Sjögren's disease will develop lymphoma, predominantly B cell non-Hodgkin lymphomas.
The diagnosis of Sjogren's disease is generally made when dry eyes causes irritation and corneal abrasions, and dry mouth causes difficulty swallowing and dental caries. Biochemical diagnosis is based on detection of lymphocytes infiltrating the salivary glands and serum auto antibodies directed towards Ro and La. Current therapies involve the use of artificial tears and saliva as well as cholinergic drugs to enhance secretions from the few remaining glandular cells (the disclosure of the following three citations are incorporated herein by reference: Kassan, S. S., and H. M. Moutsopoulos. 2004. Clinical manifestations and early diagnosis of Sjogren syndrome. Arch Intern Med 164:1275-1284, Latkany, R. 2008. Dry eyes: etiology and management. Current Opinion in Ophthalmology 19:287-291, Thanou-Stavraki, A., and J. A. James. 2008. Primary Sjogren's syndrome: Current and prospective therapies. Seminars in Arthritis and Rheumatism 37:273-292). However, no current therapies restore salivary and lachrymal gland function because the glands are largely destroyed by the time the disease is identified. It would therefore be of great benefit to be able to diagnose Sjogren's disease early since that is when it is amenable for treatment, but no such diagnostic methods exist. Thus, there is an ongoing and unmet need for improved methods for diagnosing Sjogren's disease, and in particular for use in diagnosis before the diseases progresses to a point where current therapeutic approaches are inadequate.